In the body, inert chemicals are often enzymatically converted into highly reactive and toxic electrophilic metabolites, many of which are mutagenic and carcinogenic. NADPH-cytochrome c (P-450) reductase, various forms of cytochrome P-450, and epoxide hydratase are all known to play critical roles in the enzymatic bioactivation of chemical carcinogens and other xenobiotics. This laboratory has developed and successfully employed exquisitely sensitive and specific qualitative and semi-quantitative immunohistochemical techniques with which we have been able to investigate the cellular localizations and distributions of these enzymes in a number of tissues. We now wish to broaden these studies to include the exocrine pancreas, a target for chemically-induced cancer. Employing our immunohistochemical techniques together with more classical enzyme histochemical and biochemical methods, we propose to determine which cell types within the exocrine pancreas contain the reductase, P-450s, and epoxide hydratase, to investigate the xenobiotic-metabolizing capabilities of acinar and ductal cells, to examine the inducibilities of these enzymes within exocrine pancreatic cells, and to determine possible alterations in the cellular localizations and distributions of these enzymes within the exocrine pancreas during the development of 7,12-dimethylbenz (a) anthracene- and N-nitrosobis (2-oxopropyl) amine-induced exocrine pancreatic cancer. The information provided by these investigations will allow for a much more thorough understanding of the biochemical basis for the pathogenesis of chemically-induced exocrine pancreatic cancer.